Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes.
Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes.
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DOI：
10.1038/s41419-017-0009-4
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发表时间：
2018-01-18
影响因子：
9
通讯作者：
Beer HD
中科院分区：
文献类型：
--
作者：
Sand J;Haertel E;Biedermann T;Contassot E;Reichmann E;French LE;Werner S;Beer HD
炎症体是一种多聚体蛋白质复合体，在感受到各种应激因素后聚集在一起。它们的形成导致Caspase-1介导的促炎细胞因子IL-1β和-18的激活和分泌，从而诱导炎症反应。炎症是由一种溶解的细胞死亡形式支持的，称为下垂。天然免疫细胞，如巨噬细胞或树突状细胞，表达并激活炎性小体。然而，也有研究表明，人的原代角质形成细胞在体外可以激活不同类型的炎性小体，例如，在紫外线照射或病毒感染时。角质形成细胞是表皮的主要细胞类型，是人体最外层，由复层的多层上皮构成的保护性屏障。在人类中，NLRP1基因的功能获得突变会导致由角质形成细胞中炎症小体激活所介导的综合征，其特征是皮肤炎症和皮肤癌易感性。在这里，我们证明了小鼠角质形成细胞不会激活炎性小体来响应刺激，而刺激诱导了人角质形成细胞分泌IL-1β和-18。而小鼠角质形成细胞产生Caspase-1和ProIL-18，而炎症体蛋白Nlrp1、Nlrp3、Aim2、Asc和ProIL-1β的表达与人角质形成细胞或小鼠树突状细胞相比很低，甚至检测不到。用通常用于诱导原IL-1β和炎症体蛋白表达的细胞因子启动小鼠角质形成细胞并不能挽救炎症体的激活。然而，中波紫外线诱导的炎症和中性粒细胞在小鼠皮肤中的募集依赖于IL-1、β和Caspase-1。然而，同样在这些条件下，我们没有检测到角质形成细胞表达ProIL-1β，而是检测到免疫细胞表达ProIL-1。这些结果表明，与小鼠角质形成细胞相比，人具有更高的免疫活性，这反映在应激诱导的炎性小体介导的IL-1β的分泌上。因此，人类皮肤中的角质形成细胞可以发挥免疫功能，而这些功能是由小鼠皮肤中的专业免疫细胞来执行的。
Inflammasomes are multimeric protein complexes that assemble upon sensing of a variety of stress factors. Their formation results in caspase-1-mediated activation and secretion of the pro-inflammatory cytokines pro-interleukin(IL)-1β and -18, which induce an inflammatory response. Inflammation is supported by a lytic form of cell death, termed pyroptosis. Innate immune cells, such as macrophages or dendritic cells, express and activate inflammasomes. However, it has also been demonstrated that human primary keratinocytes activate different types of inflammasomes in vitro, for example, upon UVB irradiation or viral infection. Keratinocytes are the main cell type of the epidermis, the outermost layer of the body, and form a protective barrier consisting of a stratified multi-layered epithelium. In human, gain-of-function mutations of the NLRP1 gene cause syndromes mediated by inflammasome activation in keratinocytes that are characterised by skin inflammation and skin cancer susceptibility. Here we demonstrate that murine keratinocytes do not activate inflammasomes in response to stimuli, which induce IL-1β and -18 secretion by human keratinocytes. Whereas murine keratinocytes produced caspase-1 and proIL-18, expression of the inflammasome proteins Nlrp1, Nlrp3, Aim2, Asc, and proIL-1β was, compared to human keratinocytes or murine dendritic cells, very low or even undetectable. Priming of murine keratinocytes with cytokines commonly used for induction of proIL-1β and inflammasome protein expression did not rescue inflammasome activation. Nevertheless, UVB-induced inflammation and neutrophil recruitment in murine skin was dependent on IL-1β and caspase-1. However, also under these conditions, we did not detect expression of proIL-1β by keratinocytes in murine skin, but by immune cells. These results demonstrate a higher immunological competence of human compared to murine keratinocytes, which is reflected by stress-induced IL-1β secretion that is mediated by inflammasomes. Therefore, keratinocytes in human skin can exert immune functions, which are carried out by professional immune cells in murine skin.
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影响因子：
30.8
作者：
Jin, Ying;Andersen, Genevieve;Yorgov, Daniel;Ferrara, Tracey M.;Ben, Songtao;Brownson, Kelly M.;Holland, Paulene J.;Birlea, Stanca A.;Siebert, Janet;Hartmann, Anke;Lienert, Anne;van Geel, Nanja;Lambert, Jo;Luiten, Rosalie M.;Wolkerstorfer, Albert;van der Veen, J. P. Wietze;Bennett, Dorothy C.;Taieb, Alain;Ezzedine, Khaled;Kemp, E. Helen;Gawkrodger, David J.;Weetman, Anthony P.;Koks, Sulev;Prans, Ele;Kingo, Kulli;Karelson, Maire;Wallace, Margaret R.;McCormack, Wayne T.;Overbeck, Andreas;Moretti, Silvia;Colucci, Roberta;Picardo, Mauro;Silverberg, Nanette B.;Olsson, Mats;Valle, Yan;Korobko, Igor;Boehm, Markus;Lim, Henry W.;Hamzavi, Iltefat;Zhou, Li;Mi, Qing-Sheng;Fain, Pamela R.;Santorico, Stephanie A.;Spritz, Richard A.
通讯作者：
Spritz, Richard A.
影响因子：
158.5
作者：
Jin, Ying;Mailloux, Christina M.;Spritz, Richard A.
通讯作者：
Spritz, Richard A.
影响因子：
10.4
作者：
ECKERT, RL;RORKE, EA
通讯作者：
RORKE, EA
影响因子：
9.2
作者：
Feldmeyer, Laurence;Keller, Martin;Beer, Hans-Dietmar
通讯作者：
Beer, Hans-Dietmar
影响因子：
6.5
作者：
Achachi, Amine;Vocanson, Marc;Gueniche, Audrey
通讯作者：
Gueniche, Audrey